Association of plasma n-6 and n-3 polyunsaturated fatty acids with synovitis in the knee: the MOST study

In osteoarthritis (OA) the synovium is often inflamed and inflammatory cytokines contribute to cartilage damage. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory effects whereas omega-6 polyunsaturated fatty acids (n-6 PUFAs) have, on balance, proinflammatory effects. The goal of our study was to assess the association of fasting plasma phospholipid n-6 and n-3 PUFAs with synovitis as measured by synovial thickening on contrast enhanced (CE) knee MRI and cartilage damage among subjects in the Multicenter Osteoarthritis Study (MOST). MOST is a cohort study of individuals who have or are at high risk of knee OA. An unselected subset of participants who volunteered obtained CE 1.5T MRI of one knee. Synovitis was scored in six compartments and a summary score was created. This subset also had fasting plasma, analyzed by gas chromatography for phospholipid fatty acid content, and non-CE MRI, read for cartilage morphology according to the Whole-Organ Magnetic Resonance Imaging Score (WORMS) method. The association between synovitis and cartilage morphology and plasma PUFAs was assessed using logistic regression after controlling for the effects of age, sex, and BMI. 472 out of 535 subjects with CE MRI had complete data on synovitis, cartilage morphology and plasma phospholipids. Mean age was 60 years, mean BMI 30, and 50% were women. We found an inverse relation between total n-3 PUFAs and the specific n-3, docosahexaenoic acid with patellofemoral cartilage loss, but not tibiofemoral cartilage loss or synovitis. A positive association was observed between the n-6 PUFA, arachidonic acid, and synovitis. In conclusion, systemic levels of n-3 and n-6 PUFAs which are influenced by diet, may be related to selected structural findings in knees with or at risk of OA. Future studies manipulating the systemic levels of these fatty acids may be warranted to determine the effects on structural damage in knee OA.     

Omega-3 polyunsaturated fatty acids and proxies of cardiovascular disease in hemodialysis: a prospective cohort study

BACKGROUND: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) have antithrombotic, lipid-lowering and antiinflammatory properties. The aim of this study was to verify if dietary supplementation with omega-3 PUFAs is able to induce changes of blood pressure, nutritional and coagulative profile, inflammation and blood cell counts in patients on hemodialysis (HD). METHODS: We designed a 12-month, prospective, single-blind, sequential intervention, cohort study. All of the HD patients undergoing HD in our unit were eligible for the study. Patients on HD for at least 6 months with an autologous vascular access were enrolled. No thresholds for blood pressure or lab parameters were considered. Patients taking nonsteroidal antiinflammatory drugs, steroids or statins or those with catheters, grafts, liver diseases, malignancies, malnutrition or sepsis were excluded. After the baseline evaluations the patients underwent 3 consecutive 4-month study periods taking the following supplements: A (olive oil: 2 g/day), B (omega-3 PUFA: 2 g/day), C (olive oil: 2 g/day). RESULTS: Twenty-four patients met the inclusion criteria. All patients completed the follow-up. Fibrinogen, hemoglobin, platelet, red and white blood cell counts, parathormone (PTH), partial thromboplastin time (PTT), serum total cholesterol, triglycerides, apolipoprotein A and B, C-reactive protein (CRP) and albumin levels did not change significantly during the study. On the contrary, systolic (mean +/- SD) (A: 131 +/- 17.8 mm Hg; B: 122 +/- 12.8 mm Hg; C: 129 +/- 13.2 mm Hg), diastolic (A: 83 +/- 16.3 mm Hg; B: 72 +/- 14.8 mm Hg; C: 79 +/- 6.5 mm Hg) and mean blood pressure (A: 99 +/- 16.8 mm Hg; B: 88 +/- 14.1 mm Hg; C: 96 +/- 8.7 mm Hg) were significantly lower at the end of study period B (repeated measures ANOVA and Tukey's post hoc test: p<0.05). CONCLUSIONS: In our experience, blood pressure was the only parameter influenced by omega-3 PUFA supplementation in patients on long-term HD.     

Effects of N-3 PUFAs supplementation on insulin resistance and inflammatory biomarkers in hemodialysis patients

AIMS/HYPOTHESIS: It was suggested that polyunsaturated n-3 fatty acids (n-3 PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in overall population. This study investigates a possible effect of n-3 PUFAs supplementation on the insulin sensitivity and some inflammatory markers; hence, patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are presented with insulin resistance. METHODS: This study explored the ratio between red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components of metabolic syndrome (MeS) in 35 patients (mean age 54.50 +/- 11.99 years) with CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation (EPA+DHA, 2.4 g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6, and hsCRP were examined. RESULTS: Supplementation increased EPA and DHA levels in RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio tended to be lower after supplementation (p = 0.31), but not significantly. Data revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum insulin and calculated IR index-IR HOMA were reduced after supplementation (p = 0.001 for both). There was a significant decrease in the levels of all inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane phospholipid fatty acids on inflammation markers was also registered. The changes in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF alpha. CONCLUSION: It was concluded that the EPA and DHA moderate dose administration in the patients with CRF on MHD had a beneficial effect on insulin resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were also presented.     

Effects of N-3 PUFAs Supplementation on Insulin Resistance and Inflammatory Biomarkers in Hemodialysis Patients

Aims/Hypothesis. It was suggested that polyunsaturated n-3 fatty acids (n-3 PUFAs) could improve insulin sensitivity and have an anti-inflammatory effects in overall population. This study investigates a possible effect of n-3 PUFAs supplementation on the insulin sensitivity and some inflammatory markers; hence, patients with chronic renal failure (CRF) on maintenance hemodialysis (MHD) are presented with insulin resistance. Methods. This study explored the ratio between red blood cells (RBC) phospholipid long chain fatty acids (LC FAs) and components of metabolic syndrome (MeS) in 35 patients (mean age 54.50 ± 11.99 years) with CRF on MHD. Furthermore, the effects of omega-3 FA eight-week's supplementation (EPA+DHA, 2.4g/d) on the MeS features and inflammatory markers TNF-alpha, IL 6, and hsCRP were examined. Results. Supplementation increased EPA and DHA levels in RBCs (p = 0.009 for EPA and p = 0.002 for DHA). Total n-6 PUFAs: n-3 PUFAs ratio tended to be lower after supplementation (p = 0.31), but not significantly. Data revealed a significant decrease of saturated FAs (SFA) (p = 0.01) as well as total SFA: n-3 PUFAs ratio during the treatment (p = 0.04). The values of serum insulin and calculated IR index-IR HOMA were reduced after supplementation (p = 0.001 for both). There was a significant decrease in the levels of all inflammatory markers (p = 0.01 for TNF alpha, p = 0.001 for IL 6, p = 0.001 for hsCRP, and p = 0.01 for ferritin). In multivariate regression analysis, only the changes in n-6 PUFAs: n-3 PUFAs ratio independently contributed to 40% of the variance in IR HOMA. The impact of changes in PUFAs level in RBCs membrane phospholipid fatty acids on inflammation markers was also registered. The changes in n-6: n-3 PUFAs ratio independently contributed to 18% of the variance in TNF alpha. Conclusion. It was concluded that the EPA and DHA moderate dose administration in the patients with CRF on MHD had a beneficial effect on insulin resistance decrease. The anti-inflammatory effects of the supplemented PUFAs were also presented.     

ω-3多不饱和脂肪酸诱导人胃癌细胞凋亡的实验研究

目的观察ω-3多不饱和脂肪酸(ω-3PUFAs)对SGC-7901人胃癌细胞系凋亡的影响并探究其机制。方法采用四甲基偶氮唑蓝(MTT)法、细胞形态学、DNA电泳和流式细胞技术对细胞生长与凋亡进行观察和分析,利用荧光探针rhodamine123检测线粒体跨膜电位,酶联免疫吸附法分析线粒体和胞质中细胞色素C的分布,气相色谱分析线粒体膜磷脂构成。结果二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)能显著抑制胃癌细胞的生长,诱发细胞凋亡,并呈现时间和剂量依赖性关系。40μg/mlEPA和DHA作用细胞24h后,线粒体跨膜电位显著降低(P<0.001),线粒体膜间细胞色素C大量释入胞质,EPA和DHA在线粒体膜磷脂构成中的比例迅速升高(P<0.001),而花生四烯酸(20:4ω-6,AA)占总磷脂的比例明显降低,由对照组的30.8%分别下降为20.9%和18.6%。结论ω-3PUFAs通过诱导细胞凋亡抑制胃癌细胞的生长,线粒体膜构成和功能的改变可能是ω-3PUFAs诱导凋亡的重要机制。     

The Effect of Omega-3 Fatty Acid Supplementation on the Inflammatory Response to eccentric strength exercise

Omega-3 fatty acids (omega-3) have anti-inflammatory properties. However, it is not known if omega-3 supplementation attenuates exercise-induced inflammation. We tested the hypothesis that omega-3 supplementation reduces inflammation that is induced by eccentric arm curl exercise. Healthy adult men and women (n=11; 35 ± 10 y) performed eccentric biceps curls on two occasions, once after 14d of dietary omega-3 restriction (control trial) and again after 7d of 3,000 mg/d omega-3 supplementation (omega-3 trial). Before and 48 h after eccentric exercise, signs of inflammation was assessed by measuring soreness ratings, swelling (arm circumference and arm volume), and temperature (infrared skin sensor). Arm soreness increased (p < 0.0001) in response to eccentric exercise; the magnitude of increase in soreness was 15% less in the omega-3 trial (p = 0.004). Arm circumference increased after eccentric exercise in the control trial (p = 0.01) but not in the omega-3 trial (p = 0.15). However, there was no difference between trials (p = 0.45). Arm volume and skin temperature did not change in response to eccentric exercise in either trial. These findings suggest that omega-3 supplementation decreases soreness, as a marker of inflammation, after eccentric exercise. Based on these findings, omega-3 supplementation could provide benefits by minimizing post-exercise soreness and thereby facilitate exercise training in individuals ranging from athletes undergoing heavy conditioning to sedentary subjects or patients who are starting exercise programs or medical treatments such as physical therapy or cardiac rehabilitation.

Key points

• Dietary supplementation with omega-3 fatty acids has been shown to reduce inflammation in numerous inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease, and Chrohn’s disease.
• Although strenuous exercise is known to cause acute increases in inflammation, it is not clear if omega-3 fatty acid supplementation attenuates this adverse response to exercise.
• Our research demonstrates that 3000 mg·d-1 omega-3 fatty acid supplementation minimizes the severe, delayed-onset muscle soreness that results from strenuous eccentric strength exercise.
• This information, along with a plethora of information showing that omega-3 fatty acid supplementation has other health benefits, demonstrates that a readily available over the counter nutritional supplement (i.e. omega-3 fatty acids) reduces delayed-onset soreness caused by strenuous strength exercise.
• This information has obvious relevance to athletic populations but also to other groups such as physical therapy patients and newly admitted cardiac rehabilitation patients, as muscle soreness, if left unchecked, can slow the progress in adapting to a new exercise program.
• Furthermore, as inflammation is known to be involved in the pathogenesis if numerous diseases, including heart disease, cancer, and diabetes, it is likely prudent for individuals to use inflammation-attenuating interventions, such as omega-3 supplementation, to keep inflammatory responses to physical activity at a minimum.

Key words: Fish oil, muscle soreness, eicosapentaenoic acid, docosahexaenoic acid     

Stellenwert von langkettigen Omega-3-Fettsäuren bei Prostatakrebs

The benefits of long chain polyunsaturated omega-3 fatty acids (n-3 PUFA) from fish or administered as supplements remain controversial regarding prostate cancer (PCa). Based on the currently available evidence no clear benefit of n-3 PUFA intake to generally reduce PCa incidence has been found. On the other hand n-3 PUFAs have a clear influence on the development of already existing PCa. The intake of n-3-PUFAs considerably reduces the risk of metastasis and PCa-related mortality.     

Supplementation with n-3 and n-6 polyunsaturated fatty acids: effects on lipoxygenase activity and clinical symptoms of pruritus in hemodialysis patients.

OBJECTIVE: To investigate the effect of supplementation with different sources of oils rich in long chain fatty acids, ie, fish oil (FO) and safflower oil (SO), on the production of leukotriene B4 (LTB4) by polymorphonuclear leukocytes (PMNLs) in hemodialysis patients and the consequent effects on the symptoms of pruritus. DESIGN: Randomized, prospective, double-blind study for 2 treatment groups. SETTING: Three Medical Center-affiliated units. PATIENTS: Twenty-two patients on maintenance hemodialysis, of both sexes, age > or = 20 years with complaint of dry and/or itchy skin. INTERVENTION: Two groups of patients receiving daily supplements of 6 g ethyl ester of FO or SO for 16 weeks. MAIN OUTCOME MEASURES: Red blood cell (RBC) fatty acid profile, LTB 4 production by PMNLs, and pruritus symptoms at baseline and after supplementation. RESULTS: After supplementation, the FO group had a higher RBC 22:6n3, total n-3 fatty acids, and ratio of total n-3 to total n-6 fatty acids (P < .05) than the SO group. The change in LTB4 production (pg/mL) from baseline to week 16 was 240.7 +/- 200.2 to 29.2 +/- 14.6 in the FO group and from 171.1 +/- 121.7 to 31.9 +/- 14.7 in the SO group. The overall pruritus score change was 16.7 +/- 11.4 to 8.9 +/- 9.2 in the FO group and from 17.5 +/- 8.8 to 13.1 +/- 5.6 in the SO group. FO supplementation did not result in a significant specific effect on LTB4 production by the PMNLs. There was a nonsignificant decrease in the pruritus scores that could be clinically significant and important to patients suffering with this condition. CONCLUSION: Supplementation with FO results in significant incorporation of n-3 fatty acids in the RBCs. Intervention with both FO and SO resulted in a nonsignificant improvement of clinical symptoms of pruritus and a nonsignificant reduction in LTB 4 production by PMNLs in the hemodialysis patients. The percent decrease in total puritus score was greater for the FO group compared with the SO group.     

Preoperative chemoradiation followed by transanal excision for rectal cancer

BACKGROUND: Omega-3 fatty acids (n-3 FA) demonstrate significant anti-inflammatory properties thought to occur through three principal mechanisms; (1) displacement of arachidonic acid from the cellular membrane, (2) differential prostaglandin E2 (PGE2) and LTB4 production, and (3) molecular level alterations such as diminished nuclear factor kappa B and AP-1 activation. Recently, n-3 FA have been demonstrated to significantly decrease nitric oxide (NO) production in a lipopolysaccharide (LPS)-stimulated M Phi model. We hypothesized that decreased NO production by n-3 FA occurs through inhibition of cyclooxygenase-2 (COX-2) derived PGE2 and that repletion of the system with PGE2 would obliterate these effects. Selective COX-2 inhibitor (L-748,731) experiments and separate PGE2 repletion studies were used to test this hypothesis. METHODS: NO production was assessed following 24 h with or without LPS/PGE2 in the presence of n-3 FA, L-748,731 (a selective COX-2 inhibitor), or combination (n-3 FA + L-748,731) treatment. Western blots were used to assess inducible NO synthase protein expression. RESULTS: Independently or in the presence of LPS, treatment with a COX-2 inhibitor significantly increased NO production compared with control, n-3 FA, and combination treatment. NO production in combination treatment is slightly increased compared to n-3 FA treatment. In control cells treated with LPS, PGE2 repletion resulted in a significant decrease in NO. All other treatment groups repleted with PGE2 demonstrated no significant alterations in NO production. Inducible NO synthase protein expression levels were similar to NO production across all treatments. CONCLUSION: These experiments disproved our original hypothesis that the decrease in NO production associated with n-3 FA treatment occurs through a COX-2 derived PGE2 dependent mechanism. Eliminating COX-2 derived PGE2 by a selective inhibitor actually increased NO production. Exogenous PGE2 repletion did not restore the system. Therefore, mechanisms other than n-3 FA associated alterations in COX-2 derived PGE2 are likely involved in decreasing NO production in LPS stimulated M Phi.     

Marine n-3 PUFA protects hearts from I/R injury via restoration of mitochondrial function

Abstract

Objectives. Overwhelming evidence shows that dietary supplementation with n-3 polyunsaturated fatty acids (PUFAs) elicits protective effects on patients with cardiovascular disease. However, the detailed mechanisms underlying n-3 PUFA-mediated cardioprotection are unknown, and examined in the present study. Methods: We evaluated heart performances with Langendorff perfusion apparatus. Meanwhile, whole mitochondria were purified from non-perfused hearts for functional assessment, and lipid peroxidation level was measured as well. Results. Compared with control groups, hearts from n-3 PUFA-supplemented rats showed improved functional recovery and reduced tissue injury following ischemia/reperfusion (I/R). Furthermore, the mitochondrial function of PUFA-treated hearts was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity. In addition, thiobarbituric acid-reactive substance or TBARS assay revealed that lipid peroxidation product, malondialdehyde or MDA, in the mitochondria was significantly reduced by PUFA treatment. Conclusion. Taken together, our data indicate that marine n-3 PUFA could improve cardiac performance after I/R injury by restoring mitochondrial respiratory activities and attenuating lipid peroxidation.     

Effect of n-3 fatty acids on nutritional status and inflammatory markers in haemodialysis patients

AIMS: Nutrition as an aetiological factor participates a great deal in premature atherosclerosis in haemodialysis (HD) patients. The basic mechanisms of end-stage renal disease and premature atherosclerosis are connected with changes in cell functions at the membrane level. We investigated the red cell membrane fatty acids and the effects of fish oil supplements on nutritional status and inflammatory markers in HD patients. METHODS: We examined 42 HD patients (mean age 55 +/- 8 years). The control group consisted of 16 healthy subjects of similar age and sex to the tested group. HD patients were administered supplements with 2.4 g of n-3 polyunsaturated fatty acids per day for 2 months. Before and after supplementation, we examined plasma lipids, cell membrane erythrocyte phospholipids content, serum albumin, haemoglobin, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha). RESULTS: Baseline values in the tested group confirmed the presence of essential fatty acids deficiency. A statistically significant negative correlation between TNF-alpha and eicosapentaenoic acid (EPA) (r = -0.497; P < 0.05) and IL-6 and EPA (r = -468; P = 0.03) was found in HD patients before supplementation. There was a significant increase in docosahexaenoic acids, high density lipoprotein cholesterol, plasma albumin, haemoglobin levels in HD patients after supplementation (P = 0.0001). There was a significant increase in EPA (P = 0.01) after treatment, and there was a significant decrease in inflammatory markers (IL-6 and TNF-alpha, P = 0.0001) after supplementation in the tested group. CONCLUSION: A dietary regime with fish oil could be used in dialysis patients to slow down the development of atherosclerosis and improve nutritional parameters.     

Effect of hemodialysis session on the dynamics of carnitine ester profile changes in l-carnitine pretreated end-stage renal disease patients

Purpose

Carnitine deficiency is common in end-stage renal disease (ESRD) patients receiving hemodialysis (HD) treatment. We investigated the effects of l-carnitine supplementation on acyl carnitine (AC) profile and the changes of distinct ACs during a single HD session in long-term l-carnitine pretreated ESRD patients.

Methods

Twenty non-diabetic adult patients and 37 healthy controls were studied. Blood samples were drawn before and after 12 weeks of carnitine supplementation, then hourly during an HD session, as well as 30 min after the end of the session. Free and individual AC plasma levels were determined by using ESI MS/MS technique.

Results

HD patients showed lower free- and total carnitine levels and elevated ACs and acyl/free carnitine ratio before carnitine supplementation. The l-carnitine supplementation resulted in dramatic elevation of all carnitine esters. The HD session induced a progressive decline in free, short-chain, and dicarboxylic ACs (~80 % of pre-HD amount was washed out); the decrease of medium-chain ACs proved to be more moderate (~60 % washed out), whereas the long-chain ACs remained unaffected. Already 30 min after HD, a substantial increase was seen in free carnitine concentration (reaching 26 % of predialysis level) and the ACs also started to replenish (to 21–52 % of predialysis levels), without further exogenous carnitine load.

Conclusions

The washout induced by HD session results in variable depletion of short-, medium-, and long-chain carnitine esters in carnitine-pretreated patients; the recovery of the circulating carnitine esters from the body stores occurs within 30 min after the cessation of the HD procedure.     

Eicosapentaenoic acid reduces pulmonary edema in endotoxemic rats

BACKGROUND: Recently, eicosapentaenoic acid (EPA) was found to have an anti-inflammatory effect attributable to diminished synthesis of arachidonic acid metabolites that initiate acute lung injury. We evaluated the ability of dietary EPA supplementation to prevent endotoxin-induced acute lung injury in rats. MATERIALS ANS METHODS: Rats fed a standard diet were divided randomly into two groups: for 2 weeks one group additionally was fed 1000 mg/kg/day of EPA ethyl ester emulsion (EPA rats), while in the other group the diet was supplemented with vehicle alone (control rats). Fatty acid components of alveolar macrophages (AM) were measured, as well as leukotriene (LT) B(4) and LTB(5) production by AM exposed in vitro to calcium ionophore A23187. Plasma concentrations of thromboxane (Tx) B(2), a stable metabolite of TxA(2), were examined 1 h after inducing lung injury with endotoxin (2 mg/kg iv). At 6 h, wet/dry (W/D) weight ratios were calculated for the lungs to assess pulmonary edema, and neutrophils were counted in pulmonary parenchyma and peripheral blood. RESULTS: Arachidonic acid content and LTB(4) generation in AM were significantly lower in EPA rats than in controls; conversely, EPA content and LTB(5) generation in AM were significantly higher in the EPA group. Neutrophil counts in lung parenchyma and peripheral blood did not differ between groups, but W/D and plasma TxB(2) concentrations were significantly lower in EPA rats. CONCLUSIONS: EPA supplementation depressed arachidonic acid content and LTB(4) generation in AM and plasma TxB(2) in our model, leading to decreased pulmonary edema.     

Effect of treatment with omega-3 fatty acids on C-reactive protein and tumor necrosis factor-alfa in hemodialysis patients

C-reactive protein (CRP), a strong independent risk marker of cardiovascular disease (CVD), and tumor necrosis factor-alfa (TNF-α), a known pro-inflammatory cytokine, are elevated and have damaging effects in patients with chronic renal failure (CRF). Omega-3 fatty acids play an important modulatory role in inflammatory responses. The aim of this study is to review the alterations in serum levels of TNF-α, CRP and other parameters caused by omega-3 supplementation in dialysis patients. The clinical trial was performed in 37 patients with end-stage renal disease undergoing dialysis in hemodialysis centers of three university hospitals in Tabriz. Blood samples were obtained from the study patients for hemoglobin, albumin, ferritin, triglyceride, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol, TNF-α and high specific-CRP (hs-CRP) measurement. The patients received 3 g omega-3 per day for 2 months. The side-effects noticed were nausea, diarrhea and dyspepsia and undesired drug smell. The difference noted in hemoglobin, albumin, ferritin, CRP, triglyceride, total, LDL and HDL-cholesterol before and after supplementation with omega-3 fatty acid was not statistically significant (P > 0.05). However, the use of omega-3 decreased the serum levels of TNF-α significantly. We conclude that the use of 3 g of omega-3 per day caused significant decrease in serum levels of TNF-α in the dialysis population, and its use is recommended in such patients.     

Consumption of different sources of omega-3 polyunsaturated fatty acids by growing female rats affects long bone mass and microarchitecture

Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) consumption has been reported to improve bone health. However, sources of ω-3 PUFAs differ in the type of fatty acids and structural form. The study objective was to determine the effect of various ω-3 PUFAs sources on bone during growth. Young (age 28d) female Sprague-Dawley rats were randomly assigned (n=10/group) to a high fat 12% (wt) diet consisting of either corn oil (CO) or ω-3 PUFA rich, flaxseed (FO), krill (KO), menhaden (MO), salmon (SO) or tuna (TO) for 8 weeks. Bone mass was assessed by dual-energy X-ray absorptiometry (DXA) and bone microarchitecture by micro-computed tomography (μCT). Bone turnover markers were measured by enzyme immunoassay. Lipid peroxidation was measured by calorimetric assays. Results showed that rats fed TO, rich in docosahexaenoic acid (DHA, 22:6ω-3) had higher (P<0.009) tibial bone mineral density (BMD) and bone mineral content (BMC) and lower (P=0.05) lipid peroxidation compared to the CO-fed rats. Reduced lipid peroxidation was associated with increased tibial BMD (r2=0.08, P=0.02) and BMC (r2=0.71, P=0.01). On the other hand, rats fed FO or MO, rich in alpha-linolenic acid (ALA, 18:3ω-3), improved bone microarchitecture compared to rats fed CO or SO. Serum osteocalcin was higher (P=0.03) in rats fed FO compared to rats fed SO. Serum osteocalcin was associated with improved trabecular bone microarchitecture. The animal study results suggest consuming a variety of ω-3 PUFA sources to promote bone health during the growth stage.     

Immunonutrition with omega-3-fatty acids. Are new anti-inflammatory strategies in sight?

In the early phase of sepsis and SIRS an overwhelming activation of humoral and cellular mediator systems can alter vascular resistance and causes capillary leakage increasing the risk of organ dysfunction. omega-6-arachidonic acid is released from lipid pools of cellular membranes during inflammation and is metabolized to pro-inflammatory prostaglandins and leukotriens, which are key mediators in the pathogenesis of organ dysfunction. omega-3-eicosapentaenoic acid-derived lipid mediators present altered biologic effects. Thus, omega-3-fatty acid application enables anti-inflammatory intervention on the level of lipid mediators. The current article reviews experimental and clinical data on omega-3-fatty acids. Besides the decrease of pro-inflammatory mediators, fish oil supplementation lowered post operative infection rates and showed a tendency to reduce hospital stay in surgical patients. It is believed that the decreased formation of LTB4 and TXA2 during sepsis after administration of omega-3-fatty acids accounts for improved microcirculatory perfusion and declined lactate acidosis.     

A controlled trial of the effect of folate supplements on homocysteine, lipids and hemorheology in end-stage renal disease

Elevated plasma homocysteine (Hcy), dyslipidemia and hemorheological abnormalities all occur commonly in end-stage renal disease (ESRD) and are recognized risk factors for arteriosclerosis. To study the effect of folate supplementation on these factors we conducted a randomized controlled trial. Thirteen hemodialysis (HD) and 8 continuous ambulatory peritoneal dialysis (CAPD) patients received either 5 mg folic acid daily or placebo for 3 months. After 1 and 3 months, fasting blood samples were taken for Hcy, lipid profile, blood and plasma viscosity, red blood cell (RBC) osmotic fragility, plasma fibrinogen concentration and in vivo platelet aggregability. At baseline, the CAPD patients had a higher mean plasma fibrinogen concentration than the HD patients and they also tended to have higher mean plasma viscosity. Folate-treated patients showed marked increases in RBC folate and an average decrease in plasma Hcy concentration of 33%. Mean total cholesterol, LDL cholesterol and triglyceride concentrations decreased significantly in the CAPD patients who took folate. Folate had no significant effect on hemorheology. In conclusion, folate supplements in ESRD reduce plasma Hcy concentrations and may improve lipid profiles. In our patients, hemorheological abnormalities were more marked in patients on CAPD than in those on HD and were not improved by folate supplementation.     

Fatty acids platelets and oxidative markers following intravenous n-3 fatty acids administration in cystic fibrosis: An open pilot observational study.

BACKGROUND: An imbalance in the ratio of arachidonic acid and docosahexaenoic acid (DHA) was found in cystic fibrosis (CF) affected tissues and was suggested to promote inflammation. Several studies have shown that the long chain n-3 fatty acids reduced inflammatory activity while others have highlighted prooxidant activity of DHA at high concentrations. The aim of our study was to evaluate the effects of an intravenous fish-oil emulsion enriched with n-3 FA in patients with CF on plasma and platelet FA composition and peroxidation markers. METHODS: 13 patients with CF received one IV emulsion per week of 2 mL/kg fish-oil n-3 emulsion for 12 weeks. RESULTS: There was a significant increase in 20:5 n-3 and 22:6 n-3 platelet FA composition, no variation in 20:4 n-6, a decrease in n-9. There was no variation in plasma FA composition. Specific urinary markers of lipid peroxidation derived from n-3 and n-6 showed a very high level before infusion compared with usual values in healthy subjects which was not affected by treatment. A significant weight loss and a decrease in reduced glutathione were observed in adult patients. CONCLUSIONS: The intravenous administration of n-3 FA in CF patients induced a significant modification in platelet FA composition but no modification of oxidative markers. However, the weight loss and the decreased level in reduced glutathione observed in adult patients may suggest a potential deleterious activity for some patients. Further studies are necessary to determine the optimal dose and route for long chain FA administration required to reach a potential beneficial effect.     

Cellular Production of n-3 PUFAs and Reduction of n-6�Cto�Cn-3 Ratios in the Pancreatic ��-Cells and Islets Enhance Insulin Secretion and Confer Protection Against Cytokine-Induced Cell Death

OBJECTIVE

To evaluate the direct impact of n-3 polyunsaturated fatty acids (n-3 PUFAs) on the functions and viability of pancreatic β-cells.

RESEARCH DESIGN AND METHODS

We developed an mfat-1 transgenic mouse model in which endogenous production of n-3 PUFAs was achieved through overexpressing a C. elegans n-3 fatty acid desaturase gene, mfat-1. The islets and INS-1 cells expressing mfat-1 were analyzed for insulin secretion and viability in response to cytokine treatment.

RESULTS

The transgenic islets contained much higher levels of n-3 PUFAs and lower levels of n-6 PUFAs than the wild type. Insulin secretion stimulated by glucose, amino acids, and glucagon-like peptide-1 (GLP-1) was significantly elevated in the transgenic islets. When challenged with tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and γ-interferon (IFN-γ), the transgenic islets completely resisted cytokine-induced cell death. Adenoviral transduction of mfat-1 gene in wild-type islets and in INS-1 cells led to acute changes in the cellular levels of n-3- and n-6 PUFAs and recapitulated the results in the transgenic islets. The expression of mfat-1 led to decreased production of prostaglandin E₂ (PGE₂), which in turn contributed to the elevation of insulin secretion. We further found that cytokine-induced activation of NF-κB and extracellular signal–related kinase 1/2 (ERK_1/2) was significantly attenuated and that the expression of pancreatic duodenal hemeobox-1 (PDX-1), glucokinase, and insulin-1 was increased as a result of n-3 PUFA production.

CONCLUSIONS

Stable cellular production of n-3 PUFAs via mfat-1 can enhance insulin secretion and confers strong resistance to cytokine-induced β-cell destruction. The utility of mfat-1 gene in deterring type 1 diabetes should be further explored in vivo.Polyunsaturated fatty acids (PUFAs) are synthesized from the modification of saturated fatty acid precursors by different desaturases and elongation enzymes. Mammals have neither the desaturase necessary to synthesize the precursors of other PUFAs, linoleic acid (LA, n-6), and α-linolenic acid (ALA, n-3), nor the n-3 fatty acid desaturase to convert n-6 PUFAs to n-3 PUFAs. Therefore, LA and ALA and their elongation products are essential fatty acids to mammals and must be taken from diets (1,2). Physiologically, n-3 PUFAs play critical roles in the development and functions of retina, spermatozoa, and the central nervous system (1,3).A series of epidemiological studies have established the health benefits of dietary intake of n-3 PUFAs in preventing cardiovascular diseases and type 2 diabetes (4,5). Two recent large-scale clinical studies also demonstrated that long-term dietary intake of fish oil starting at 1 year of age lowers the risk of type 1 diabetes and islet autoimmunity (6,7). Consistent with such epidemiological evidence, recent studies in rodents indicated that dietary gain or direct administration of n-3 PUFAs could restore palmitate acid– or linoleic acid–impaired insulin secretion (8,9). An issue central to this study is whether the effects of n-3 PUFAs on type 1 diabetes are related to the direct impact on the functions and viability of β-cells. To evaluate such effects as well as the underlying mechanisms, we developed a transgenic mouse model that expresses a C. elegans gene, fat-1, encoding a n-3 fatty acid desaturase (10). Since this enzyme can convert n-6 PUFAs into the corresponding n-3 forms, transgenic expression of fat-1 will render the host endogenous capability of producing n-3 PUFAs while concomitantly reducing the levels of n-6 PUFAs. Using such a unique animal model, we are able to evaluate the impact of stable cellular elevation of n-3 PUFAs on insulin secretion and viability of β-cells without the need of lengthy feeding of fish oil. The positive outcomes from our studies may reveal the potential utility of this type of gene to deter and mitigate type 1 diabetes.     

Marine n-3 Polyunsaturated Fatty Acid Supplementation and Quality of Life After Kidney Transplant

Marine n-3 polyunsaturated fatty acids (PUFAs) may improve cardiovascular, renal, and mental health. No previous trial has investigated the effects of marine n-3 PUFA supplementation on quality of life (QoL) indices after renal transplant.